The photodynamic therapy (PDT) is a method that is suitable for treating tumors and premalignant changes in the skin and mucosa of various hollow organs (Juarranz et al., 2008; Agostinis et al., 2011).
The PDT is based on the interaction of three components: photosensitizer, light in the visible range, and oxygen.
After systemic or topical application of a photosensitizer, an accumulation of the photosensitizer is carried out in the malignant tissue. Using light of a suitable wavelength, the photosensitizer can be stimulated. In the stimulated state, energy is transferred to a reactant, e.g., molecular oxygen. In this case, reactive oxygen molecules are generated, which in turn damage cellular structures of the tumor tissue, by which cellular processes such as apoptosis and necrosis are introduced (Agostinis, et al., 2011; Allison and Sibata, 2010).
A more ideal photosensitizer for the PDT shows selective accumulation in tumor cells, no or minimal systemic toxicity, and it is photochemically efficient.
Hypericin 1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro (1,10,9,8-opqra)perylene-7,14-dione was already described as a potential photosensitizer in the literature (Agostinis et al., 2002).
In in-vitro studies, the effectiveness of hypericin in PDT was shown in a series of cell lines (Karioti and Bilia, 2010).
Moreover, in-vivo animal studies confirm the potential of hypericin for application in PDT (Bhuvaneswari et al., 2010; Chen et al., 2003; Liu et al., 2000; Sanovic et al., 2011).
Hypericin is hydrophobic and water-insoluble. For this reason, in the past, hypericin was brought into solution using the organic solvent dimethyl sulfoxide (DMSO) or a water-soluble polymer, polyethylene glycol (PEG).
Animal experiments in a rat model showed encouraging results with respect to the PDT of bladder carcinoma. In this case, hypericin was brought into the tumor cells using polyethylene glycol. With a hypericin dose of 30 μM and an irradiation with light (595 nm) of an intensity of 25 up to 50 mW/cm2, up to 98% of the tumor cells were killed (Kamuhabwa et al. 2003).
For a clinical application, however, a water-soluble formulation of hypericin is required, which has tumor selectivity and can be stimulated with light in the visible range.
The document WO 01/89576 A2 describes how the solubility of hypericin can be increased by the adjuvant polyvinylpyrrolidone (povidone, PVP).
The use of PVP-hypericin in PDT is also described in WO 2014/079972 A1. WO 2014/079972 A1 deals with in particular a device that can be used in the PDT of hollow organs, such as the human bladder.
PVP-hypericin shows a selective accumulation in tumor cells in vitro and in vivo (Kubin et al., 2008; Vandepitte et al., 2011).